Syntenin

Syntenin (SDCBP / syndecan-binding protein / MDA-9)

一行要約

Syndecan の cytoplasmic tail に結合する PDZ scaffold タンパクで、heparan sulfate proteoglycan (HSPG) cluster を ALIX に橋渡しすることで ESCRT-I 非依存的なエクソソーム biogenesis 経路 (syndecan – syntenin – ALIX route) を駆動する rate-limiting factor。Baietti らが 2012 年に Nat Cell Biol で同定したこの経路は、tetraspanin / ESCRT-dependent route と並ぶ第二の主要 biogenesis route として確立した。MDA-9 (melanoma differentiation associated gene-9) の別名通り、メラノーマ・グリオーマ等の転移と治療抵抗性の driver としての側面も持つ多機能因子。

主要エビデンス

Syndecan-syntenin-ALIX 経路: Baietti らはエクソソーム分泌における syntenin / ALIX の必須性を示し、heparan sulfate を持つ syndecan が exosomal cargo を集約する分子モデルを確立。syntenin / ALIX KD で exosome 分泌が顕著に減少。

腫瘍進展 (MDA-9 機能): メラノーマで MDA-9 として同定され、c-Src / FAK 活性化を介して invasion / metastasis を促進する経路が報告。グリオーマ・乳癌・前立腺癌などで MDA-9 高発現は予後不良と関連。

治療標的化: PDZ1 阻害剤 (PDZ1i) が MDA-9-syntenin の Src 活性化機能を遮断する preclinical 候補。

メカニズム

PDZ ドメイン構造: PDZ1 と PDZ2 のタンデム配置。Syndecan-1/2/3/4 の cytoplasmic C 末端 (EFYA motif) が PDZ1 に結合、ephrin / glutamate receptor / merlin 等多数の partner も結合する。

ALIX とのインターアクション: Syntenin N 末端の LYPx_nL motif (YPxL family) が ALIX V ドメインに結合し、ESCRT-III (CHMP4) リクルートメントへ橋渡しする。

Heparan sulfate dependent: syndecan ectodomain の heparan sulfate (HS) chain が exosomal cargo (FGF / VEGF / Wnt / chemokine 等) をクラスタリングし、syntenin が cytoplasmic 側で同時集約する coupling 機構。Heparan sulfate biosynthesis 阻害は exosome 分泌を低下させる。

Src 活性化軸 (MDA-9 機能): 細胞質 syntenin は c-Src と直接結合し、focal adhesion 形成と migration / invasion を駆動する。

関連エンティティ・概念

• Syndecan-syntenin-ALIX route: ALIX — 直接下流の partner
• ESCRT machinery: TSG101 — parallel canonical route
• Tetraspanin EV markers: CD9 / CD63 / CD81
• Trafficking: Rab27
• Pathway: Exosome-biogenesis-pathway
• Concept: EV-mediated-intercellular-communication / EV-organotropism / Tumor-derived-EV-cargo-biology
• MOC: cancer-extracellular-vesicles

関連論文

直近 30 件のみ表示中 (関連 64 件)。 全件は MOC ページ または Obsidian (source Markdown) から辿れます。

Basic-Extracellular vesicles

• Jones et al. BMCBioinformatics 2023 — Tidyproteomics An open-source R package and data object for quantitative proteomics post analysis and visualization
• Hudson et al. CancerLett 2026 — Human neural stem cell-derived extracellular vesicles improve cognitive function following glioma chemoradiation therapy
• Semba et al. Cancers 2020 — Lung adenocarcinoma mouse models based on orthotopic transplantation of syngeneic tumor-initiating cells expressing
• Wong et al. Cancers 2020 — Exosomal microRNAs and organotropism in breast cancer metastasis
• Cocozza et al. Cell 2020 — SnapShot Extracellular vesicles
• Gurung et al. CellCommunSignal 2021 — The exosome journey from biogenesis to uptake and intracellular signalling
• Amorim et al. Cells 2022 — Extracellular vesicles derived from MDA-MB-231 cells trigger neutrophils to a pro-tumor profile
• Matsui et al. EMBORep 2021 — ALIX and ceramide differentially control polarized small extracellular vesicle release from epithelial cells
• Larios et al. JCellBiol 2020 — ALIX-and ESCRT-III-dependent sorting of tetraspanins to exosomes
• Almeida et al. JExtracellVesicles 2022 — Urinary extracellular vesicles contain mature transcriptome enriched in circular and long noncoding RNAs with
• Blavier et al. JExtracellVesicles 2023 — The capture of extracellular vesicles endogenously released by xenotransplanted tumours induces an inflammatory
• Han et al. MolCancer 2022 — Exosome biogenesis machinery, regulation, and therapeutic implications in cancer
• Radler et al. MolTher 2023 — Exploiting the biogenesis of extracellular vesicles for bioengineering and therapeutic cargo loading
• Clancy et al. NatCellBiol 2021 — Profiling and promise of supermeres
• Kugeratski et al. NatCellBiol 2021 — Quantitative proteomics identifies the core proteome of exosomes with syntenin-1 as the highest abundant protein and a
• Arya et al. NatCellBiol 2022 — Ceramide-rich microdomains facilitate nuclear envelope budding for non-conventional exosome formation
• Palmulli et al. NatCellBiol 2024 — CD63 sorts cholesterol into endosomes for storage and distribution via exosomes
• Mathieu et al. NatCommun 2021 — Specificities of exosome versus small ectosome secretion revealed by live intracellular tracking of CD63 and CD9
• El-Shennawy et al. NatCommun 2022 — Circulating ACE2-expressing extracellular vesicles block broad strains of SARS-CoV-2
• Shen et al. NatCommun 2026 — Co-enrichment of proteins in extracellular vesicles
• Verweij et al. NatMethods 2021 — The power of imaging to understand extracellular vesicle biology in vivo
• Vietri et al. NatRevMolCellBiol 2020 — The many functions of ESCRTs
• vanNiel et al. NatRevMolCellBiol 2022 — Challenges and directions in studying cell-cell communication by extracellular vesicles
• Dixson et al. NatRevMolCellBiol 2023 — Context-specific regulation of extracellular vesicle biogenesis and cargo selection
• Bojmar et al. STARProtoc 2024 — Protocol for cross-platform characterization of human and murine extracellular vesicles and particles
• Jeppesen et al. TrendsCellBiol 2023 — Extracellular vesicles and nanoparticles emerging complexities

Basic-Immunotherapy

• Sehgal et al. JClinInvest 2021 — Dynamic single-cell RNA sequencing identifies immunotherapy persister cells following PD-1 blockade

Basic-Neutrophil and myeloid cell

• Nogales-Pons et al. JExpMed 2021 — Myeloid diversity in tumors shaped by genes, location, and time

Basic-Oncogene and genetics

• Nesta et al. TrendsGenet 2021 — Hotspots of human mutation

Basic-Others

• Sarni et al. NatGenet 2026 — A progeria syndrome links DNA hypermethylation to age-related pathology